Peripheral nerve injuries are common diseases that affect hundreds of thousands of patients every year. Severe nerve injuries result in the formation of a significant gap between the severed nerve stumps. When the gap is large (4 mm), autografts are commonly used as "bridges." Autograft is not ideal because their availability is limited and the patient is exposed to the morbidity of a second surgical incision. Up to the present, many approaches have been examined for enhancing peripheral nerve regeneration. However, none of them has performed better than autograft procedures, the 'gold standard'for repairing peripheral nerve injuries. At the center of this proposal is the development of nanofiber based biodegradable nerve grafts pre- seeded with Schwann cells in bioreactors for enhancing peripheral nerve regeneration to the level comparable to autograft. The fabrication of polymeric nanofibers by electrospinning has recently been used to form fibrous matrices that may closely mimic the structure of the extracellular matrix (ECM). The highly porous three- dimensional (3D) architecture of the fibrous matrix may provide beneficial control of cell attachment, migration, proliferation, differentiation, and matrix protein deposition. The attachment and migration of Schwann cells on the matrix are critical for the success of nerve regeneration. The rotating bioreactor is a form of dynamic culture designed to utilize low shear, three-dimensionality, and high mass transfer to promote ex vivo tissue synthesis. The bioreactor culture system will be helpful to fasten and improve Schwann cell growth on the artificial nerve graft. The research project will include the following phases: Aim 1: Design, fabricate and characterize a nanofiber based biodegradable nerve graft for peripheral nerve regeneration;Aim 2: Investigate Schwann cell proliferation in the microenvironment of nanofiber based biodegradable nerve graft in rotating bioreactors;Aim 3: Evaluate the Schwann cell containing nerve graft for bridging peripheral nerve gaps in an animal model in vivo. PUBLIC HEALTH RELEVANCE: Peripheral nerve injuries are common diseases that affect hundreds of thousands of patients every year. The proposed research will be helpful to aid patients with peripheral nerve injuries.